The invention relates to a method of synthesizing substituted aminocyclohexanone derivatives.
Substituted aminocyclohexanone derivatives are known from WO 2004/043967 as important intermediates in the synthesis of spirocyclic cyclohexane derivatives. It is also known that some spirocyclic cyclohexane derivatives have an affinity for the μ-opioid receptor and the ORL1 receptor and are suitable as active ingredients in drugs, in particular for the treatment of pain of disorders of the central nervous system.
The production methods described in WO 2004/043967 for synthesis of the corresponding substituted aminocyclohexanone intermediates require the use of cyanide salts.
Further production methods which include the use of cyanide salts are known from WO 2008/101660, WO 2008/009416, Lednicer, J. Med. Chem. 1981, 24, 341-346, and Lednicer, J. Med. Chem. 1979, 22, 1157-1158.
Other production methods include the use of azide salts (WO 2006/010095, WO 2006/010094, WO 2005/070407).
A further known production method includes eight synthesis stages and also requires the use of azide salts within the scope of a Curtius reaction (Lednicer et al., J. Med. Chem. 1980, 23, 424-430).
However, the use of cyanide salts or azide salts is disadvantageous, inter alia, because production on a commercial scale is hindered for reasons of occupational safety and environmental protection.
There is a need for a method of production of substituted aminocyclohexanone derivatives which affords advantages over conventional methods and which, in particular, does not require the use of cyanide salts or azide salts.